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1.
Mov Disord ; 39(8): 1364-1374, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38787806

RESUMO

BACKGROUND: Low-intensity transcranial ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) technique with high spatial specificity. Previous studies showed that TUS delivered in a theta burst pattern (tbTUS) increased motor cortex (MI) excitability up to 30 minutes due to long-term potentiation (LTP)-like plasticity. Studies using other forms of NIBS suggested that cortical plasticity may be impaired in patients with Parkinson's disease (PD). OBJECTIVE: The aim was to investigate the neurophysiological effects of tbTUS in PD patients off and on dopaminergic medications compared to healthy controls. METHODS: We studied 20 moderately affected PD patients in on and off dopaminergic medication states (7 with and 13 without dyskinesia) and 17 age-matched healthy controls in a case-controlled study. tbTUS was applied for 80 seconds to the MI. Motor-evoked potentials (MEP), short-interval intracortical inhibition (SICI), and short-interval intracortical facilitation (SICF) were recorded at baseline, and at 5 minutes (T5), T30, and T60 after tbTUS. Motor Unified Parkinson's Disease Rating Scale (mUPDRS) was measured at baseline and T60. RESULTS: tbTUS significantly increased MEP amplitude at T30 compared to baseline in controls and in PD patients on but not in PD patients off medications. SICI was reduced in PD off medications compared to controls. tbTUS did not change in SICI or SICF. The bradykinesia subscore of mUPDRS was reduced at T60 compared to baseline in PD on but not in the off medication state. The presence of dyskinesia did not affect tbTUS-induced plasticity. CONCLUSIONS: tbTUS-induced LTP plasticity is impaired in PD patients off medications and is restored by dopaminergic medications. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Potencial Evocado Motor , Córtex Motor , Plasticidade Neuronal , Doença de Parkinson , Humanos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Potencial Evocado Motor/fisiologia , Potencial Evocado Motor/efeitos dos fármacos , Córtex Motor/fisiopatologia , Plasticidade Neuronal/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Estudos de Casos e Controles , Estimulação Magnética Transcraniana/métodos , Ritmo Teta/fisiologia
2.
Ann Neurol ; 91(2): 238-252, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34964172

RESUMO

OBJECTIVE: Transcranial ultrasound stimulation (TUS) is a promising noninvasive brain stimulation technique with advantages of high spatial precision and ability to target deep brain regions. This study aimed to develop a TUS protocol to effectively induce brain plasticity in human subjects. METHODS: An 80-second train of theta burst patterned TUS (tbTUS), regularly patterned TUS (rTUS) with the same sonication duration, and sham tbTUS was delivered to the motor cortex in healthy subjects. Transcranial magnetic stimulation (TMS) was used to examine changes in corticospinal excitability, intracortical inhibition and facilitation, and the site of plasticity induction. The effects of motor cortical tbTUS on a visuomotor task and the effects of occipital cortex tbTUS on motor cortical excitability were also tested. RESULTS: The tbTUS produced consistent increase in corticospinal excitability for at least 30 minutes, whereas rTUS and sham tbTUS produced no significant change. tbTUS decreased short-interval intracortical inhibition and increased intracortical facilitation. The effects of TMS in different current directions suggested that the site of the plastic changes was within the motor cortex. tbTUS to the occipital cortex did not change motor cortical excitability. Motor cortical tbTUS shortened movement time in a visuomotor task. INTERPRETATION: tbTUS is a novel and efficient paradigm to induce cortical plasticity in humans. It has the potential to be developed for neuromodulation treatment for neurological and psychiatric disorders, and to advance neuroscience research. ANN NEUROL 2022;91:238-252.


Assuntos
Córtex Motor/efeitos da radiação , Plasticidade Neuronal/efeitos da radiação , Ritmo Teta , Ultrassom , Adulto , Mapeamento Encefálico , Excitabilidade Cortical , Potencial Evocado Motor , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibição Neural , Lobo Occipital/fisiologia , Desempenho Psicomotor/efeitos da radiação , Tratos Piramidais/efeitos da radiação , Estimulação Magnética Transcraniana , Adulto Jovem
3.
Front Neuroimaging ; 3: 1474060, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39399386

RESUMO

Objective: Spinal cord stimulation (SCS) is an invasive treatment option for patients suffering from chronic low-back pain (cLBP). It is an effective treatment that has been shown to reduce pain and increase the quality of life in patients. However, the activation of pain processing regions of cLBP patients receiving SCS has not been assessed using objective, quantitative functional imaging techniques. The purpose of the present study was to compare quantitative resting-state (rs)-fMRI and arterial spin labeling (ASL) measures between SCS patients and healthy controls and to correlate clinical measures with quantitative multimodal imaging indices in pain regions. Methods: Multi-delay 3D GRASE pseudo-continuous ASL and rs-fMRI data were acquired from five patients post-SCS with cLBP and five healthy controls. Three ASL measures and four rs-fMRI measures were derived and normalized into MNI space and smoothed. Averaged values for each measure from a pain atlas were extracted and compared between patients and controls. Clinical pain scores assessing intensity, sensitization, and catastrophizing, as well as others assessing global pain effects (sleep quality, disability, anxiety, and depression), were obtained in patients and correlated with pain regions using linear regression analysis. Results: Arterial transit time derived from ASL and several rs-fMRI measures were significantly different in patients in regions involved with sensation (primary somatosensory cortex and ventral posterolateral thalamus [VPL]), pain input (posterior short gyrus of the insula [PS]), cognition (dorsolateral prefrontal cortex [DLPC] and posterior cingulate cortex [PCC]), and fear/stress response (hippocampus and hypothalamus). Unidimensional pain rating and sensitization scores were linearly associated with PS, VPL, DLPC, PCC, and/or amygdala activity in cLBP patients. Conclusion: The present results provide evidence that ASL and rs-fMRI can contrast functional activation in pain regions of cLBP patients receiving SCS and healthy subjects, and they can be associated with clinical pain evaluations as quantitative assessment tools.

4.
Elife ; 122024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39190585

RESUMO

Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.


Assuntos
Estimulação Acústica , Potencial Evocado Motor , Córtex Motor , Estimulação Magnética Transcraniana , Humanos , Adulto , Feminino , Masculino , Estimulação Magnética Transcraniana/métodos , Potencial Evocado Motor/fisiologia , Córtex Motor/fisiologia , Adulto Jovem , Ondas Ultrassônicas
5.
Brain Stimul ; 16(4): 1135-1143, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37524296

RESUMO

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a novel non-invasive brain stimulation technique with high depth penetrance and spatial resolution. Theta-burst TUS (tbTUS) is a plasticity-inducing protocol which increases motor cortical excitability for up to 30 min following 80s of sonication. While this protocol may have therapeutic potential for the treatment of psychiatric and neurological disorders, the mechanisms of action of TUS remain unclear. OBJECTIVE: We conducted the first pharmacological study to examine the mechanisms of TUS in human primary motor cortex. By administering brain-active drugs with known mechanisms of action, we aimed to elucidate the mechanisms of tbTUS. METHODS: Fourteen healthy subjects participated in a within-subjects randomized, double-blind, cross-over study with five visits. At each visit, one of four study drugs (carbamazepine - Na+ channel blocker, nimodipine - L-type Ca2+ channel blocker, lorazepam - positive allosteric modulator of gamma-aminobutyric acid (GABA) type A receptor, dextromethorphan - N-methyl-d-aspartate receptor antagonist) or placebo was administered in random order, followed by tbTUS. RESULTS: The plasticity effects of tbTUS on motor cortex excitability measured by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation were reduced by all study drugs compared to placebo. CONCLUSION: tbTUS may induce NMDA-dependent synaptic plasticity since the effects are blocked by increased GABAA receptor activities and voltage-gated Na+ and Ca2+ channels blockers. These results are consistent with the hypotheses that tbTUS induced long-term potentiation-like mechanisms and that TUS involves activation of mechanosensitive Na+ and Ca2+ channels. Alternatively, non-specific pharmacologically induced changes in excitatory/inhibitory balance might have interfered with the effects of tbTUS.


Assuntos
Córtex Motor , Humanos , Córtex Motor/fisiologia , Estudos Cross-Over , Plasticidade Neuronal/fisiologia , Potenciação de Longa Duração/fisiologia , Potencial Evocado Motor/fisiologia , Estimulação Magnética Transcraniana/métodos
6.
Neurol Res ; 40(8): 696-701, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29663852

RESUMO

OBJECTIVE: Pain, poor sleep quality, restless legs syndrome (RLS), and other symptoms are frequently reported by patients with Parkinson's disease (PD). However, the impact that pain severity and interference has on non-motor symptoms (NMS) has not been extensively studied. The objective of the present study is to explore the relationship between sleep quality in PD to pain and other NMS that affect quality of life. METHODS: The study included 100 PD patients and 100 age and gender-matched controls assessed for pain severity and pain interference using the Brief Pain Inventory and sleep quality using the Pittsburgh Sleep Quality Index. Participants were also evaluated for their subjective levels of anxiety and depression using the Hospital Anxiety and Depression Scale. RESULTS: PD patients with poor sleep quality had greater pain severity and pain interference than controls and PD patients with good or borderline sleep quality. PD patients with poor sleep quality also had the greatest case-ness and severity for depression and anxiety. However, RLS was not significantly correlated with depression, anxiety or pain. DISCUSSION: Poor sleep quality in PD patients is related to greater pain severity, pain interference, and more radiating and paresthestic pain that is independent of RLS. There is a higher prevalence of depression and anxiety in PD patients compared to controls, especially in PD patients with poor sleep quality. Our findings suggest a relationship between poor sleep quality in PD with pain, anxiety and depression. Prospective studies are warranted to investigate the causal relationship.


Assuntos
Ansiedade , Depressão , Dor/complicações , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Sono , Idoso , Ansiedade/epidemiologia , Ansiedade/etiologia , Estudos de Casos e Controles , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Feminino , Humanos , Masculino , Dor/epidemiologia , Dor/psicologia , Medição da Dor , Doença de Parkinson/epidemiologia , Prevalência , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/psicologia
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